This work is a longue durée history of neuroscientific classification practices through the lens of handedness research, and it affirms the importance of ostensibly outmoded concepts for contemporary knowledge production. The study draws on close readings and digital analyses of publications in English, French, and German; archival collections; and oral history interviews. In 1865, Paul Broca postulated that the speech center sits in the left hemisphere of the brain and that humans are right-handed because they are left-brained. Subsequently, a virtual obsession with the causes of manual preference and its association with human identity spread throughout the mind-, brain-, and neurosciences in Europe and North America. A progression of closely entwined anatomical, physiological, genetic, hormonal, mirror-neuron-based, and epigenetic models of manual preference all rested on the idea that right-handedness is a distinctive marker of superiority both among humans and across species. With the rise of molecularization and statistical methods, scientists further transformed left-handedness into a manageable “risk” factor for nonconformity. By the late twentieth century, handedness research had become an innocuous umbrella under which to pursue inquiries into the biological underpinnings of controversial socio-medical categories. The past one and a half centuries of research on manual preference exemplify the idea that the reach of scientific classifications extends far beyond the characteristics that such classifications are supposed to categorize. The insight that handedness has functioned as a proxy for mental and physical dis/abilities, sex/gender, sexual behavior, class, and race/ethnicity challenges our concept of intersectionality and suggests that we must include even seemingly neutral categories in our considerations of governance, inclusion, and citizenship. Furthermore, the layering of theories and methodologies in handedness research offers examples of an epistemological multiplicity among diverse conceptual and experimental frameworks. Frequently incompatible ways of approaching the brain have led to a parallelism of incommensurable ideas of fixed localization and dynamic plasticity in present-day neuroscience. This multiplicity of understandings of “the brain” simultaneously leads to epistemic inconsistencies in neuroscientific theories and endows the neurosciences with a seemingly all-encompassing expertise.